POS0518 EFFECT OF FILGOTINIB (FIL) ON BODY WEIGHT (BW) AND BODY MASS INDEX (BMI) AND EFFECT OF BASELINE BMI ON THE EFFICACY AND SAFETY OF FIL IN RHEUMATOID ARTHRITIS (RA)
Authors: A. Balsa, S. Wassenberg, A. Tournadre, H. D. Orzechowski, K. Van Beneden, V. Rajendran, U. Lendl, P. J. Stiers, C. Watson, R. Caporali, P. Verschueren
Journal: Annals of the Rheumatic Diseases (2022)

Background FIL is a Janus kinase (JAK) 1 preferential inhibitor approved for the treatment (tx) of moderate to severe RA. Weight gain has been reported with other JAK inhibitors 1–3 ; it is important to describe the effect of FIL on BW/BMI for physicians to correctly inform and appropriately treat patients. Objectives Our primary aim was to assess the effect of FIL on BW/BMI using data from the FINCH 1–3 studies. Secondary aims were to assess the efficacy and safety of FIL according to baseline BMI. Methods FINCH 1–3 ( NCT02889796 , NCT02873936 , NCT02886728 ) were phase 3, randomised, double-blind, active/placebo (PBO)-controlled studies of FIL 100/200 mg (FIL100/FIL200) ± methotrexate (MTX) in patients with active RA who had an inadequate response to MTX (FINCH 1) or biologic DMARD (FINCH 2), or were MTX naïve (FINCH 3). We assessed changes from baseline (CFB) in BW and BMI by tx group and baseline BMI, and the efficacy and safety of FIL by baseline BMI (&lt;25, 25–&lt;30 or ≥30 kg/m 2 ). Efficacy measures included American College of Rheumatology (ACR)20/50/70 response, Disease Activity Score 28 with C-reactive protein (DAS28-CRP) and health assessment questionnaire disability index (HAQ-DI). Safety data were from 7 RA clinical trials (FINCH 1–4, DARWIN 1–3) 4 . Results In FINCH 1–3, baseline disease characteristics such as HAQ-DI, DAS28-CRP and clinical disease activity index were similar across BMI subgroups for each tx group. There were no clinically relevant CFB in median BW or BMI in any tx group or differences between tx groups. Mean CFB in BMI (kg/m 2 ) were 0.4 with FIL200 and FIL100 and 0.3 with adalimumab (ADA) at Week 52 in FINCH 1; 0.2, 0.6 and −0.1 with FIL200, FIL100 and PBO, respectively, at Week 24 in FINCH 2; and 0.5, 0.6, 1.1 and 0.3 with FIL200+MTX, FIL100+MTX, FIL200 and MTX, respectively, at Week 52 in FINCH 3. CFB in BMI did not appear dependent on baseline BMI. FIL200±MTX was efficacious vs controls regardless of baseline BMI for most measures at each timepoint. In FINCH 1, in the &lt;25, 25–&lt;30 and ≥30 kg/m 2 BMI subgroups, DAS28-CRP &lt;2.6 was achieved by 38%, 29% and 33% of the FIL200 group, 29%, 19% and 21% of the ADA group, and 7%, 10% and 11% of the PBO group at Week 12, respectively. Figure 1 shows ACR20 responders by baseline BMI in FINCH 1–3. Integrated safety data across baseline BMI subgroups are summarised in Table 1. VTE rate was numerically higher with FIL200 in the ≥30 than 25–&lt;30 or &lt;25 kg/m 2 BMI subgroups; serious infection rate was numerically higher with FIL100 in the &lt;25 mg/m 2 subgroup vs other BMI subgroups. Table 1. Exposure-adjusted incidence rate (95% CI) of AEs per 100 PYE by baseline BMI FIL dose (mg) BMI (kg/m 2 ) &lt;25 25–&lt;30 ≥30 PYE 3062.8 PYE 2640.1 PYE 2382.2 TEAEs 200 34.5 (32.0, 37.1) 35.7 (33.0, 38.6) 36.6 (33.7, 39.8) 100 44.3 (40.4, 48.6) 43.0 (38.9, 47.5) 45.3 (41.1, 50.0) Serious TEAEs 200 5.3 (4.4, 6.4) 5.8 (4.8, 7.1) 7.1 (5.8, 8.5) 100 7.6 (6.0, 9.4) 6.5 (5.0, 8.4) 8.1 (6.4, 10.2) Deaths 200 0.3 (0.2, 0.7) 0.5 (0.3, 1.0) 0.5 (0.2, 1.0) 100 0.4 (0.1, 1.0) 0.3 (0.1, 1.0) 0.2 (0.1, 0.9) Venous thrombotic and embolic events 200 0.1 (0.0, 0.4) 0.1 (0.0, 0.5) 0.5 (0.2, 1.0) 100 0.1 (0.0, 0.7) 0.1 (0.0, 0.8) 0.2 (0.1, 0.9) Major adverse cardiovascular events 200 0.3 (0.2, 0.7) 0.3 (0.1, 0.7) 0.5 (0.2, 1.0) 100 0.6 (0.3, 1.3) 0.3 (0.1, 1.0) 0.6 (0.2, 1.4) Serious infections 200 1.1 (0.7, 1.7) 1.7 (1.2, 2.5) 1.8 (1.2, 2.6) 100 2.6 (1.8, 3.9) 1.2 (0.7, 2.2) 2.2 (1.4, 3.4) Herpes zoster 200 1.6 (1.1, 2.2) 1.4 (1.0, 2.1) 1.8 (1.2, 2.6) 100 1.0 (0.5, 1.8) 1.2 (0.7, 2.2) 1.0 (0.5, 2.0) Malignancy excluding nonmelanoma skin cancer 200 0.5 (0.3, 1.0) 0.7 (0.4, 1.3) 0.5 (0.3, 1.1) 100 0.6 (0.3, 1.3) 0.4 (0.2, 1.2) 0.8 (0.4, 1.7) BMI, body mass index; FIL, filgotinib; PYE, patient years of exposure; (TE)AE, (treatment-emergent) adverse event Conclusion FIL did not substantially affect CFB in BW or BMI. FIL200±MTX was generally more efficacious vs controls regardless of baseline BMI, and the rate of TEAEs was similar across baseline BMI subgroups. References [1]Tofacitinib SmPC [2]Baracitinib SmPC [3]Upadacitinib SmPC [4]Winthrop K, et al. ACR 2021. Abstract 1698 Acknowledgements The FINCH studies were funded by Gilead Sciences (Foster City, CA, United States). We thank the physicians and patients who participated in the studies. Medical writing support was provided by Debbie Sherwood, BSc (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV (Mechelen, Belgium). Disclosure of Interests Alejandro Balsa Speakers bureau: AbbVie, Galapagos, Gilead, Lilly, Nordic, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Galapagos, Lilly, Nordic, Pfizer, and UCB, Grant/research support from: AbbVie, Pfizer, UCB, Siegfried Wassenberg Speakers bureau: AbbVie, MSD, Pfizer, and Sanofi, Consultant of: AbbVie, Gilead, Lilly, Nichi-Iko, Pfizer, and UCB, Grant/research support from: Pfizer, Anne Tournadre Speakers bureau: Fresenius-Kabi and Sanofi, Paid instructor for: Fresenius-Kabi, Consultant of: AbbVie, Fresenius-Kabi, Lilly, Novartis, and Sanofi, Grant/research support from: Novartis, Pfizer, and UCB, Hans-Dieter Orzechowski Employee of: Galapagos, Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, Vijay Rajendran Employee of: Galapagos, Udo Lendl Employee of: Galapagos, Pieter-Jan Stiers Shareholder of: Galapagos, Employee of: Galapagos, Chris Watson Shareholder of: Galapagos, Employee of: Galapagos, Roberto Caporali Speakers bureau: AbbVie, Accord, BMS, Celltrion, Fresenius-Kabi, Galapagos, Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Accord, BMS, Celltrion, Fresenius-Kabi, Galapagos, Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB, Patrick Verschueren Speakers bureau: Eli Lilly, Galapagos, MSD, and Roularta, Consultant of: AbbVie, BMS, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Pfizer, Sidekick Health, and UCB, Grant/research support from: Pfizer Chair Management of Early Rheumatoid Arthritis at KU Leuven Belgium.